Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors

The Ca2+-binding protein calmodulin (CaM) has been shown to bind directly to cytoplasmic domains of some G protein-coupled receptors, including the dopamine D2 receptor. CaM binds to the N-terminal portion of the long third intracellular loop of the D2 receptor, within an Arg-rich epitope that is al...

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Autores: Navarro Brugal, Gemma, Aymerich, María Soledad, Marcellino, Daniel, Cortés Tejedor, Antonio, Casadó, Vicent, Mallol Montero, Josefa, Canela Campos, Enric I. (Enric Isidre), 1949-, Agnati, Luigi F., Woods, Amina S., Fuxe, Kjell, Lluís i Biset, Carme, Lanciego, José Luis, Ferré, Sergi, Franco Fernández, Rafael
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/122461
Acceso en línea:https://hdl.handle.net/2445/122461
Access Level:acceso abierto
Palabra clave:Adenosina
Proteïnes
Adenosine
Proteins
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spelling Interactions between calmodulin, adenosine A2A, and dopamine D2 receptorsNavarro Brugal, GemmaAymerich, María SoledadMarcellino, DanielCortés Tejedor, AntonioCasadó, VicentMallol Montero, JosefaCanela Campos, Enric I. (Enric Isidre), 1949-Agnati, Luigi F.Woods, Amina S.Fuxe, KjellLluís i Biset, CarmeLanciego, José LuisFerré, SergiFranco Fernández, RafaelAdenosinaProteïnesAdenosineProteinsThe Ca2+-binding protein calmodulin (CaM) has been shown to bind directly to cytoplasmic domains of some G protein-coupled receptors, including the dopamine D2 receptor. CaM binds to the N-terminal portion of the long third intracellular loop of the D2 receptor, within an Arg-rich epitope that is also involved in the binding to Gi/o proteins and to the adenosine A2A receptor, with the formation of A2A-D2 receptor heteromers. In the present work, by using proteomics and bioluminescence resonance energy transfer (BRET) techniques, we provide evidence for the binding of CaM to the A2A receptor. By using BRET and sequential resonance energy transfer techniques, evidence was obtained for CaM-A2A-D2 receptor oligomerization. BRET competition experiments indicated that, in the A2A-D2 receptor heteromer, CaM binds preferentially to a proximal C terminus epitope of the A2A receptor. Furthermore, Ca2+ was found to induce conformational changes in the CaM-A2A-D2 receptor oligomer and to selectively modulate A2A and D2 receptor-mediated MAPK signaling in the A2A-D2 receptor heteromer. These results may have implications for basal ganglia disorders, since A2A-D2 receptor heteromers are being considered as a target for anti-parkinsonian agents.American Society for Biochemistry and Molecular Biology2009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/122461Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1074/jbc.M109.034231Journal of Biological Chemistry, 2009, vol. 284, num. 41, p. 28058-28068https://doi.org/10.1074/jbc.M109.034231(c) American Society for Biochemistry and Molecular Biology, 2009info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1224612026-05-27T06:46:51Z
dc.title.none.fl_str_mv Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
title Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
spellingShingle Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
Navarro Brugal, Gemma
Adenosina
Proteïnes
Adenosine
Proteins
title_short Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
title_full Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
title_fullStr Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
title_full_unstemmed Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
title_sort Interactions between calmodulin, adenosine A2A, and dopamine D2 receptors
dc.creator.none.fl_str_mv Navarro Brugal, Gemma
Aymerich, María Soledad
Marcellino, Daniel
Cortés Tejedor, Antonio
Casadó, Vicent
Mallol Montero, Josefa
Canela Campos, Enric I. (Enric Isidre), 1949-
Agnati, Luigi F.
Woods, Amina S.
Fuxe, Kjell
Lluís i Biset, Carme
Lanciego, José Luis
Ferré, Sergi
Franco Fernández, Rafael
author Navarro Brugal, Gemma
author_facet Navarro Brugal, Gemma
Aymerich, María Soledad
Marcellino, Daniel
Cortés Tejedor, Antonio
Casadó, Vicent
Mallol Montero, Josefa
Canela Campos, Enric I. (Enric Isidre), 1949-
Agnati, Luigi F.
Woods, Amina S.
Fuxe, Kjell
Lluís i Biset, Carme
Lanciego, José Luis
Ferré, Sergi
Franco Fernández, Rafael
author_role author
author2 Aymerich, María Soledad
Marcellino, Daniel
Cortés Tejedor, Antonio
Casadó, Vicent
Mallol Montero, Josefa
Canela Campos, Enric I. (Enric Isidre), 1949-
Agnati, Luigi F.
Woods, Amina S.
Fuxe, Kjell
Lluís i Biset, Carme
Lanciego, José Luis
Ferré, Sergi
Franco Fernández, Rafael
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Adenosina
Proteïnes
Adenosine
Proteins
topic Adenosina
Proteïnes
Adenosine
Proteins
description The Ca2+-binding protein calmodulin (CaM) has been shown to bind directly to cytoplasmic domains of some G protein-coupled receptors, including the dopamine D2 receptor. CaM binds to the N-terminal portion of the long third intracellular loop of the D2 receptor, within an Arg-rich epitope that is also involved in the binding to Gi/o proteins and to the adenosine A2A receptor, with the formation of A2A-D2 receptor heteromers. In the present work, by using proteomics and bioluminescence resonance energy transfer (BRET) techniques, we provide evidence for the binding of CaM to the A2A receptor. By using BRET and sequential resonance energy transfer techniques, evidence was obtained for CaM-A2A-D2 receptor oligomerization. BRET competition experiments indicated that, in the A2A-D2 receptor heteromer, CaM binds preferentially to a proximal C terminus epitope of the A2A receptor. Furthermore, Ca2+ was found to induce conformational changes in the CaM-A2A-D2 receptor oligomer and to selectively modulate A2A and D2 receptor-mediated MAPK signaling in the A2A-D2 receptor heteromer. These results may have implications for basal ganglia disorders, since A2A-D2 receptor heteromers are being considered as a target for anti-parkinsonian agents.
publishDate 2009
dc.date.none.fl_str_mv 2009
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/122461
url https://hdl.handle.net/2445/122461
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.M109.034231
Journal of Biological Chemistry, 2009, vol. 284, num. 41, p. 28058-28068
https://doi.org/10.1074/jbc.M109.034231
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 2009
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 2009
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Bioquímica i Biomedicina Molecular)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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